Novel CXCL18b emerges as a key pro-apoptotic regulator from genome-wide study of the CXC chemokine system in yellow catfish under hypoxia and bacterial challenge.

The CXC chemokine system is fundamental to vertebrate immune defense, yet its evolutionary diversity and functional adaptations in non-model teleost species facing complex environmental stressors are largely unexplored. Here, we present a genome-wide identification of the CXC chemokine system in the economically important yellow catfish (Pelteobagrus fulvidraco), revealing 15 CXCL and 9 CXCR genes. Evolutionary analyses revealed these genes are under strong purifying selection yet exhibit lineage-specific expansion, including teleost-specific duplicates. They displayed spatially divergent expression patterns across healthy tissues, with enrichment in immune organs such as spleen, kidney, gill, and intestine. Furthermore, these genes showed dynamic, tissue-specific transcriptional responses to hypoxia and bacterial challenge including Aeromonas hydrophila and Aeromonas veronii, highlighting their role in environmental adaptation. Most importantly, functional investigation of a novel gene, CXCL18b, unveiled its essential apoptotic role during hypoxic stress. siRNA-mediated knockdown of CXCL18b led to the altered expression of apoptosis-related genes (including MyD88) and decreased hepatocyte apoptosis, suggesting a potential transcriptional link between CXCL18b and the apoptotic program. This discovery not only deepens our understanding of the molecular mechanisms underlying hypoxic tolerance in fish but also provides a promising target for genetic improvement of stress-resistant aquaculture strains. Our study provides the first comprehensive resource on the CXC chemokine system in yellow catfish and establishes CXCL18b as a crucial mediator of hypoxic tolerance, offering new insights for breeding stress-resilient aquaculture species.