From skin to brain: Herpesvirus in cetaceans as an emerging systemic pathogen and ocean health sentinel

Introduction
Herpesvirus (HV) infections in cetaceans are increasingly recognized as indicators of health disturbances due to their association with immunosuppression, stress, and co-infections. However, its full clinical and ecological significance remains underexplored.

Our research in this field compiles and analyzes findings from stranded cetaceans in the Western Mediterranean, offering critical insights into herpesvirus tropism and pathology, emergence in new hosts, and its relevance in One Health frameworks.

Methods
Over 1,000 post-mortem tissue samples from 49 cetaceans, representing five different species, stranded between 2010 and 2022 were analyzed using conventional PCR, sequencing, and histopathology. HV RNA detection was employed to assess viral replication.

Results

• Ecological expansion: an overall prevalence of 80.85% was reported in a 2021 cohort of 47 stranded cetaceans in the Valencian Community, which was the highest recorded to date. Additionally, Alphaherpesvirus (AHV) was identified in a Mediterranean-stranded humpback whale (Megaptera novaeangliae)—the first such report in the region and only the second globally. These findings suggest both wide circulation and an expanded host range.
• Tropism: HV was detected in diverse tissues—skin, genital mucosa, and notably, the central nervous system (CNS). Gammaherpesvirus (GHV) sequences were associated with CNS inflammation and meningitis, representing the first evidence of neurotropism in odontocetes.
• Clinical pathology: HV-associated lesions ranged from proliferative to ulcerative and inflammatory changes. Some animals exhibited histological lesions with active HV replication in the absence of overt clinical signs.
• Genetic diversity and replication: most sequences belonged to GHV, while AHV showed greater genetic heterogeneity. RNA detection confirmed active replication, particularly in juveniles and neonates—supporting age-related susceptibility.

Conclusions
Our integrated assessment identifies HV as a complex, multi-organ pathogen with underrecognized impacts on cetacean health and conservation. Integrating HV surveillance within a One Health framework will enhance our capacity to detect early signs of marine ecosystem disruption through sentinel species like cetaceans.