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It remains unclear, however, whether this extends to the within\u2010host regulatory environment and what the consequences are for reinfecting pathogens. Here, we asked whether prior pathogen exposure of hosts induces gene expression heterogeneity in host and\/or pathogen during infection. We quantified gene expression in\u00a0vivo following a high\u2010dose challenge of house finches (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Haemorhous mexicanus<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) previously given controlled, varied exposures to a bacterial pathogen (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Mycoplasma gallisepticum<\/jats:italic>\n                    <\/jats:styled-content>\n                    ). To measure gene expression heterogeneity, we collected transcriptomic data from two host tissues (conjunctiva and spleen), and simultaneously, from pathogen at the primary site of infection (conjunctiva). In conjunctiva, but not spleen, prior pathogen exposure induced significant heterogeneity in host gene expression relative to pathogen\u2010na\u00efve hosts, even when accounting for effects of sex. Hosts given a lower versus higher prior exposure dose showed the greatest within\u2010group heterogeneity in expression during re\u2010challenge. Functional enrichment analyses for significantly variable host genes indicated an over\u2010representation of terms involved in the immune response among birds with prior exposure. Infecting pathogen from the conjunctiva followed similar heterogeneity patterns, with more heterogeneous expression among pathogens infecting previously exposed hosts than those infecting na\u00efve hosts. While the mechanisms underlying these patterns remain unresolved, our results indicate that prior exposure induces a within\u2010host environment that promotes heterogeneous gene expression across both hosts and pathogens. This suggests that gene expression variation in host and pathogen should be considered alongside sequence variation to understand the coevolutionary dynamics of infectious diseases.\n                  <\/jats:p>","DOI":"10.1111\/mec.70319","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T04:36:14Z","timestamp":1774413374000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Host Prior Exposure Augments Gene Expression Heterogeneity of Both Host and Pathogen During In\u00a0Vivo Infection"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-1872","authenticated-orcid":false,"given":"Anna A.","family":"P\u00e9rez\u2010Umphrey","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathobiology &amp; Veterinary Science University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2682-5145","authenticated-orcid":false,"given":"Edan R.","family":"Tulman","sequence":"additional","affiliation":[{"name":"Department of Pathobiology &amp; Veterinary Science University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Garrett\u2010Larsen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3572-9494","authenticated-orcid":false,"given":"Michal","family":"Vinkler","sequence":"additional","affiliation":[{"name":"Department of Zoology Faculty of Science, Charles University  Prague Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Langwig","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Geary","sequence":"additional","affiliation":[{"name":"Department of Pathobiology &amp; Veterinary Science University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Adelman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Memphis  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9573-2914","authenticated-orcid":false,"given":"Dana M.","family":"Hawley","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyu192"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3491"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsbl.2013.0594"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jav.01058"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-44503-X_27"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/1365-2656.12511"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-9993.2001.01070.pp.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-0420.2005.00440.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1890\/12-2010.1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000619"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tree.2007.09.008"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318628111"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/648672"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.137583"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-294X.2012.05551.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1974.10482955"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10682-022-10175-8"},{"key":"e_1_2_10_20_1","unstructured":"Carlson M. andH.Pag\u00e8s.2023.\u201cAnnotationForge: Tools for Building SQLite\u2010Based Annotation Data. 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