¹State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, CHINA DOI : 10.9775/kvfd.2025.33698 Feline panleukopenia virus (FPV) is an extremely contagious pathogen that induces severe vomiting, diarrhea, and dehydration in cats, often resulting in high mortality rates and substantial economic losses. Host responses are crucial for viral entry, replication, assembly, and disease progression, despite so much is not known, especially regarding the interactions between hosts and viruses. Herein, we employed the FPV strain FPVXJ- 04, which was previously isolated and characterized by our team in Xinjiang, China. To perform a comparative transcriptomic analysis of the gene expression profile in Crandell-Reese feline kidney (CRFK) cells following infection with the FPV-XJ-04 strain. Following infection of CRFK cells with the FPV-XJ-04 strain, the differentially expressed genes in CRFK cells were predicted to be involved in several key signaling pathways, including the TNF signaling pathway, IL-17 signaling pathway, cytokinecytokine receptor interaction, Toll-like receptor signaling pathway, MAPK signaling pathway, and RIG-I-like receptor signaling pathway. In addition, the immune response was significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, we highlight 11 key genes in the TNF signaling pathway that are associated with host defense response to the invasion of FPV-XJ-04 strain. This research provides valuable insights into the gene transcription processes within immune cells, elucidating the pathways critical to the early stages of infection pathogenesis. Keywords : Feline Panleukopenia Virus, Host-virus interactions, Immune response, Comparative transcriptomic analysis, TNF signaling pathway