Repeated pathogen-specific testing may lead to the premature exclusion of a viral aetiology when pathogen abundance is low or detection is restricted to a narrow diagnostic window. This represents a particular challenge in field investigations, where clinical signs and gross pathological findings are often non-specific and compatible with multiple infectious and non-infectious conditions.
During a haemorrhagic disease outbreak in farmed Alsatian char, repeated pathogen-specific RT-PCR testing failed to detect the suspected viral agent despite sampling shortly after the reported onset of clinical signs. Affected fish showed haemorrhagic lesions involving skeletal and cardiac muscle tissues. Based on conventional diagnostic testing alone, these findings could have redirected the investigation towards alternative infectious, metabolic or environmental causes.
Transcriptomic analysis of cardiac tissue, however, revealed a pronounced host-response pattern consistent with antiviral immune activation. Additional sequence-level evidence within the transcriptomic dataset further supported continued investigation of a viral aetiology. Although these findings were not considered sufficient for definitive pathogen identification, they provided an independent molecular rationale for maintaining the original diagnostic hypothesis.
Targeted virological investigation was therefore continued, and subsequent sampling confirmed the presence of the suspected viral pathogen, with the result independently verified by an external virology laboratory.
This case demonstrates the potential value of host-response transcriptomics as a complementary diagnostic tool when direct pathogen detection is inconsistent. Rather than replacing pathogen-specific assays, transcriptomic information can provide critical diagnostic direction and help prioritize further investigation in complex disease outbreaks.