Viral nervous necrosis is a significant threat to healthy fish culture, characterized by central nervous system and ocular lesions that involve critical immune mechanisms. The aim of this study was to elucidate the immune complexity associated with viral nervous necrosis to enhance understanding of the immune interactions between viral nervous necrosis and Trachinotus ovatus. In this study, bioinformatics techniques were used to analyze differentially expressed genes (DEGs) and immune-disease related pathways in the asymptomatically infected and symptomatic groups following a natural outbreak of viral nervous necrosis, and the DEGs identified in this study differentiated asymptomatically infected from symptomatic individuals, highlighting the importance of the immune response in the progression of the disease. Notably, gene ontology (GO) entries that were significantly upregulated in the brain tissue of the asymptomatically infected group included those related to the cellular response to cycloheximide, which inhibits the de novo synthesis of viral proteins, leading to viral death. The strong correlation between DEGs and immune response in this study clarifies the complex role of immunity in viral nervous necrosis and provides a data base for analyzing specific functions and pathways following outbreaks of this disease.