{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:47:16Z","timestamp":1785422836802,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,24]]},"group-title":"Ecology","reference-count":87,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R01GM144972"],"award-info":[{"award-number":["R01GM144972"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"award":["LUAUS24184"],"award-info":[{"award-number":["LUAUS24184"]}],"id":[{"id":"https:\/\/ror.org\/037n8p820","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Variability in acquired protection, whether from prior pathogen exposure or vaccination, is increasingly recognized as a key determinant of host population-level variation in disease traits. It remains unclear whether this extends to the within-host physiological environment and what the consequences are for reinfecting pathogens. Here, we asked whether prior pathogen exposure of hosts induces gene expression heterogeneity in the host and\/or pathogen during infection. We quantified gene expression\n                  <jats:italic>in vivo<\/jats:italic>\n                  following high-dose pathogen challenge of house finches (\n                  <jats:italic>Haemorhous mexicanus<\/jats:italic>\n                  ) previously given controlled, varied exposure histories to a bacterial pathogen (\n                  <jats:italic>Mycoplasma gallisepticum<\/jats:italic>\n                  ; MG). To measure gene expression heterogeneity, we collected transcriptomic data from two host tissues (conjunctiva and spleen), and, simultaneously, from pathogen infecting the primary site of infection (conjunctiva). In the conjunctiva, but not the spleen, prior pathogen exposure induced significant heterogeneity in host gene expression relative to pathogen-na\u00efve hosts. Further, hosts that received a lower prior exposure dose rather than a higher primary dose showed the greatest within-group heterogeneity in expression during re-challenge. Functional enrichment analyses for significantly variable host genes indicated an over-representation of terms involved in the immune system\u2019s response to pathogens, namely a diversified inflammatory response, in birds with prior pathogen exposure. The infecting pathogen from the conjunctiva followed similar patterns of heterogeneity in host gene expression, where pathogen infecting hosts with prior exposure had more heterogeneous expression than those infecting pathogen-na\u00efve hosts. While the exact mechanisms that underlie greater variation in gene expression cannot be resolved by this study, our results are consistent with the hypothesis that prior host exposure induces a within-host environment that promotes heterogeneous gene expression across both hosts and pathogens. This suggests that to understand the coevolutionary dynamics of infectious diseases we must consider not only the genetic sequence variation, but also gene expression variation in host and pathogen.\n                <\/jats:p>","DOI":"10.1101\/2025.08.20.671316","type":"posted-content","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T04:10:15Z","timestamp":1756095015000},"source":"Crossref","is-referenced-by-count":0,"title":["Host prior exposure augments heterogeneity in gene expression in both host and pathogen during\n                  <i>in vivo<\/i>\n                  infection"],"prefix":"10.64898","author":[{"given":"Anna A.","family":"P\u00e9rez-Umphrey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edan R.","family":"Tulman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Garrett-Larsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3572-9494","authenticated-orcid":false,"given":"Michal","family":"Vinkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Langwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Geary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Adelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana M.","family":"Hawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025082803551137000_2025.08.20.671316v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyu192"},{"key":"2025082803551137000_2025.08.20.671316v1.2","doi-asserted-by":"crossref","unstructured":"Adelman, J. 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