Available online 4 September 2025

Strong selection on chromosome 23 enriches nervous system development and neuronal resilience.

slc25a11 at WDRES-9 links mitochondrial metabolism to neural pathology resistance.

Gunnison River Rainbow Trout resistance reflects conserved WDRES-9 hotspots across strains.

CD209 (DC-SIGN) shows selection and post-infection upregulation, key in recognition and resistance.

Genomic–transcriptomic integration shows innate defenses act early, adaptive dominate later.

Whirling disease is a debilitating disease of Rainbow Trout caused by Myxobolus cerebralis. The parasite invasion leads to skeletal deformities, neurological impairment, and high mortality. Since its introduction to North America, M. cerebralis has severely impacted wild trout populations in several regions. In this study, we focus on a promising Whirling disease-resistant Rainbow Trout strain developed in the Gunnison River, Colorado. We analyzed the genomes and transcriptomes of this resistant strain at different time points after challenge with M. cerebralis. Signature selection analysis revealed several regions across the genome under selection, with the highest density found on chromosome 23. Several genes found in areas under selection are associated with neuron differentiation and nervous system development. Also, several immuno-genes were under selection, including several with relevance to the innate and adaptive immune response. The transcriptomic analysis revealed that the Gunnison River Rainbow Trout develops a comprehensive immune response after exposure to M. cerebralis. This is supported by the significant enrichment of specific immune response pathways, including differentiation and activation of B-cells and T-cells. These results suggest that certain immune pathways are likely to participate in building the Gunnison River Rainbow Trout’s early, mid, and long-term immune response against M. cerebralis, while other pathways related to nervous system development may help juvenile fish survive the effects of Whirling disease. The transcriptomic analysis also reveals that more than half of the top 20 upregulated immune genes are components of the complement pathway. Notably, CD209 (DC-SIGN), a critical gene involved in antigen recognition and dendritic cell function, is among the most highly upregulated genes. The results also indicate the presence of a specific region on chromosome 9 in this strain, previously linked to resistance to this disease. This may explain this strain’s strong disease resistance and survival capacity in natural environments.

Gunnison River Rainbow Trout

Whirling disease-resistant

Genomic analysis

Transcriptomic analysis

Signature selection

Gene expression profile

© 2025 The Author(s). Published by Elsevier Ltd on behalf of Australian Society for Parasitology.