Chile is the world’s second-largest producer of Atlantic salmon ( Salmo salar), with aquaculture playing a key role in the economic development. However, the industry faces ongoing challenges to fish health and productivity, including pathogenic infections and environmental stressors like hypoxia. As part of their defense strategy, Atlantic salmon deploy nutritional immunity, regulating iron availability to restrict pathogen growth. This mechanism becomes especially relevant under hypoxic conditions, where iron homeostasis intersects with oxygen-sensing pathways such as the hypoxia-inducible factor (HIF) signaling . Previous studies have demonstrated that the recombinant ferritin-based vaccine candidate IPath® can modulate iron metabolism and reduce mortality from marine pathogens.
This study investigated the effect of IPath ® vaccination in Atlantic salmon subjected to sublethal hypoxia and subsequently challenged with Vibrio ordalii . Fish were allocated to vaccinated and unvaccinated (control) groups, exposed to normoxia –hypoxia cycles, and finally infected with V. ordalii. Blood parameters and histological analyses of kidney and gill tissues were evaluated. T ranscriptomic profiling (RNA-seq) of Atlantic salmon head kidney was performed.
Phenotypic and histopathological analyses revealed that IPath®-vaccinated fish displayed enhanced hypoxia tolerance, characterized by increased erythrocyte and hemoglobin levels (Figure 1) , reduced gill and kidney damage, and improved immune responsiveness. Differential gene expression analysis revealed significant upregulation of genes involved in the HIF-1 signaling pathway, iron homeostasis, and immune response, particularly in vaccinated fish under hypoxic conditions.
These results suggest that IPath® modulates hypoxia-responsive transcriptional programs and iron metabolism, contributing to improved physiological resilience and immunocompetence. These findings support the use of ferritin-based vaccination strategies to enhance the capacity of Atlantic salmon to withstand environmental stress and pathogen exposure in marine farming systems.
Funding: FONDAP #1523A0007.