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The geographic extent and taxonomic scale of AIWS meant events leading up to the outbreak were heterogeneous, multifaceted, and oftentimes unobserved; progression from morbidity to death was rapid, leaving few tell\u2010tale symptoms. Here, we take a forensic genomic approach to discover candidate genes that may help explain sea star wasting syndrome. We report the first genome and annotation for <jats:italic>Pisaster ochraceus<\/jats:italic>, along with differential gene expression (DGE) analyses in four size classes, three tissue types, and in symptomatic and asymptomatic individuals. We integrate nucleotide polymorphisms associated with survivors of the wasting disease outbreak, DGE associated with temperature treatments in <jats:italic>P. ochraceus<\/jats:italic>, and DGE associated with wasting in another asteroid <jats:italic>Pycnopodia helianthoides<\/jats:italic>. In <jats:italic>P. ochraceus<\/jats:italic>, we found DGE across all tissues, among size classes, and between asymptomatic and symptomatic individuals; the strongest wasting\u2010associated DGE signal was in pyloric caecum. We also found previously identified outlier loci co\u2010occur with differentially expressed genes. In cross\u2010species comparisons of symptomatic and asymptomatic individuals, consistent responses distinguish genes associated with invertebrate innate immunity and chemical defence, consistent with context\u2010dependent stress responses, defensive apoptosis, and tissue degradation. Our analyses thus highlight genomic constituents that may link suspected environmental drivers (elevated temperature) with intrinsic differences among individuals (age\/size, alleles associated with susceptibility) that elicit organismal responses (e.g., coelomocyte proliferation) and manifest as sea star wasting mass mortality.<\/jats:p>","DOI":"10.1111\/mec.15386","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T17:39:20Z","timestamp":1582047560000},"page":"1087-1102","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["An initial comparative genomic autopsy of wasting disease in sea stars"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7282-0380","authenticated-orcid":false,"given":"Dannise V.","family":"Ruiz\u2010Ramos","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Sciences University of California Merced CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-5426","authenticated-orcid":false,"given":"Lauren M.","family":"Schiebelhut","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences University of California Merced CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7333-8390","authenticated-orcid":false,"given":"Katharina J.","family":"Hoff","sequence":"additional","affiliation":[{"name":"Institute for Computer Science and Mathematics University of Greifswald Greifswald Germany"},{"name":"Center for Functional Genomics of Microbes University of Greifswald Greifswald Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1827-0669","authenticated-orcid":false,"given":"John P.","family":"Wares","sequence":"additional","affiliation":[{"name":"Department of Genetics and the Odum School of Ecology 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