Equine herpesvirus type 8 (EHV-8), a member of the alpha herpesvirus subfamily, is a significant pathogen in donkeys, causing abortion and respiratory infections, which result in considerable economic losses within the equine industry. Despite its importance, limited research has been conducted on the molecular response to EHV-8 in donkeys. The present study investigated the host cell response to EHV-8 infection in Rabbit kidney (RK-13) cells through transcriptomic and proteomic approaches. Our findings identified several candidate genes and proteins, along with their associated signaling pathways, involved in the cellular response to EHV-8 infection in this in vitro model. However, because RK-13 cells may not accurately replicate viral-host interactions in equine species, additional in vivo studies in horses and donkeys are necessary to achieve a more thorough understanding of viral pathogenesis in these animals.