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While several studies have examined the genetic basis for parasite resistance, the role of epigenetics in the immune response to parasites is less understood. Yet, epigenetic modifications, such as changes in DNA methylation, may allow species to respond rapidly to parasite prevalence or virulence. To test the role of DNA methylation in relation to parasite infection, we examined genome\u2010wide DNA methylation before and during infection by a parasitic nematode, <jats:italic>Syngamus trachea<\/jats:italic>, in a natural population of house sparrows (<jats:italic>Passer domesticus<\/jats:italic>) using reduced representation bisulfite sequencing (RRBS). We found that DNA methylation levels were slightly lower in infected house sparrows, and we identified candidate genes relating to the initial immune response, activation of innate and adaptive immunity, and mucus membrane functional integrity that were differentially methylated between infected and control birds. Subsequently, we used methylation\u2010sensitive high\u2010resolution melting (MS\u2010HRM) analyses to verify the relationship between methylation proportion and <jats:italic>S.\u00a0trachea<\/jats:italic> infection status at two candidate genes in a larger sample dataset. We found that methylation level at <jats:italic>NR1D1<\/jats:italic>, but not <jats:italic>CLDN22<\/jats:italic>, remained related to infection status and that juvenile recruitment probability was positively related to methylation level at <jats:italic>NR1D1<\/jats:italic>. This underscores the importance of performing follow\u2010up studies on candidate genes. Our findings demonstrate that plasticity in the immune response to parasites can be epigenetically mediated and highlight the potential for epigenetic studies in natural populations to provide further mechanistic insight into host\u2013parasite interactions.<\/jats:p>","DOI":"10.1002\/ece3.9539","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T06:36:33Z","timestamp":1669617393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Infection by a helminth parasite is associated with changes in <scp>DNA<\/scp> methylation in the house sparrow"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-6208","authenticated-orcid":false,"given":"Sarah L.","family":"Lundregan","sequence":"first","affiliation":[{"name":"Department of Biology, Centre for Biodiversity Dynamics Norwegian University of Science and Technology  Trondheim 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