Abstract / Summary
Abstract White-tailed deer are susceptible hosts for SARS-CoV-2, exhibiting robust viral replication, active shedding, efficient deer-to-deer transmission, and widespread natural infection across the United States. However, the molecular level host responses remain poorly defined. In this study, we describe whole blood transcriptomes from experimentally infected deer and compare their responses with other previously published wildlife hosts such as elk and bison, to better understand the molecular mechanisms underlying infection. Over time, deer exhibited a regulated antiviral response, with rapid activation of innate immune pathways and Coronavirus Pathogenesis signaling as early as day 2 post infection (pi), followed by prevalent transcriptomic remodeling and inhibition of cytokine storm associated pathways at day 5 pi, and a reduction in differentially expression by day 7 pi. Ingenuity Pathway Analysis highlighted early induction of interferon associated networks and hypercytokinemia related signaling. Comparative analysis with elk and bison revealed 22 conserved upregulated genes at day 2 pi, including antiviral regulators such as ADAR and STAT1 . At day 5 pi, five downregulated genes and 20 upregulated genes remained conserved between the species, highlighting a lack of shared molecular responses across species, in line with divergent infection susceptibilities. Together, these findings define the temporal architecture of the deer immune response and identify conserved host defense mechanisms serving as molecular markers of SARS-CoV-2 infection in wildlife.