Scombrids represent some of the most economically important fisheries globally. However, increased interest in creating aquaculture systems for these fish has increased the risk of disease emergence. One such disease, Puffy Snout Syndrome (PSS), causes collagenous tissue growths on the face, in numerous scombrid taxa. PSS has only been documented in captive-held fish populations and can lead to high mortality rates. Despite this, little is known about PSS's causative agent(s) and the immune response they elicit. Therefore, we leveraged metatranscriptomic data of symptomatic-captive, asymptomatic-captive, and healthy-wild Pacific Mackerel (Scomber japonicus) to evaluate the physiological characteristics of PSS infections and identify a mechanism of disease. PSS symptomatic-captive and asymptomatic-captive mackerel showed distinct gene expression patterns from their wild counterparts. Genes involved in tumorigenesis, immune response, and pathophysiology were over-expressed in captive-held fish. In particular, the Wnt9 pathway was increased by more than 2 orders of magnitude in captive fish, potentially representing a diagnostic feature of this disease. Together, these host physiological data and our past visual identification of RNA virus-like particles in afflicted tissues suggest that viral-mediated oncogenesis may be driving PSS in captive mackerel.