Transcriptomic profiling of wild Atlantic salmon affected with red skin disease (RSD)

Red skin disease (RSD) is an emerging disease affecting wild Atlantic salmon characterised by petechial ventral haemorrhaging. A causative agent has not yet been confirmed. To identify signalling and metabolic pathways affected by RSD, wild-caught Atlantic salmon skin sections were subjected to RNA-Seq in a NextSeq 550 instrument. Transcriptome analysis of RSD-affected salmon revealed activation of pattern-recognition receptors NOD-1, RIG-1, and TLRs such as tlr8 and tlr13, and the upregulation of interferon-stimulated genes such as E3 ubiquitin/ISG15 ligase TRIM25 and ISG15-like protein. Skin lesions showed activation of NF-κB pathway, upregulation of proinflammatory cytokines (ltb4 receptor 1-like, tsg-6, il6ra, mip2a, and saa5), and cell receptors (cxcr4 and cxcr2) likely attracting lymphocytes and neutrophils. Activation of the complement system was likely regulated by the alternative pathway and factor H. In severe RSD-lesions, molecular pathways related to oxidative phosphorylation and steroid metabolism were activated, with strong upregulation of the glucose-6-phosphate 2 gene involved in glucose release. Pathological changes such as ferroptosis and porphyrin were observed, likely as a result of haemodilution and hypoxia previously noted in RSD. The activation of pathogen-associated molecular patterns and antiviral responses in RSD strongly suggests the presence of an infectious agent associated directly or indirectly with RSD. This study contributes to a better understanding of RSD pathology in Atlantic salmon.