As a pivotal node species between ray-finned fish and teleost, Acipenseriformes retain partial ancestral genetic signatures while exhibiting enhanced disease resistance among extant farmed fish. The molecular mechanisms underlying their unique specific genes remain poorly characterized. Through OrthoFinder-based comparative genomics sturgeon and teleost, our study establishing a species-specific gene library comprising 1,246 orthologous clusters. Integrated analysis of four NCBI-released infection transcriptomes identified 579 immune-related specific genes, with notable enrichment in NF-κB, RIG-I-like receptor, and NOD-like receptor signaling pathways. Among these, 81 genes including NAIP, CASP1, and ASC formed a core regulatory network. T-cloning, qRT-PCR, and overexpression experiments were employed to demonstrated Siberian sturgeon NAIP/NLRC4 role in mediating inflammatory. They responses through complex formation that triggers IL-1β release and pyroptosis. These findings establish NAIP/NLRC4 as a phylogenetically ancient immunoregulator that triggers inflammatory cascades, offering novel targets for disease-resistant breeding.

NAIP,NLRC4,Acipenseriformes,Anti-infection immunity,Orthologous,Inflammatory cascades