Falcon plasma proteomics to improve avian aspergillosis diagnosis

Aspergillosis is a respiratory disease in birds, particularly falcons, often diagnosed late due to nonspecific signs and limited performance of current diagnostic tools. This study aimed to identify novel plasma biomarkers for aspergillosis comparing plasma samples from 15 healthy falcons and 15 affected falcons (9 with early and 6 with advanced aspergillosis). First, the presence of the causative agent, Aspergillus fumigatus, was ruled out through a proteotyping strategy. Proteomic profiling using data-independent acquisition mass spectrometry further identified 861 avian proteins. In advanced infection, 50 host proteins were significantly modulated in terms of abundance, including acute-phase proteins such as the haptoglobin isoform X2, alpha-1-acid glycoprotein, and serum amyloid A-like protein. Several immunoglobulin isoforms and functionally uncharacterized proteins were also differentially abundant. In contrast, no significant changes were observed between healthy and early affected birds. Comparison between early and advanced cases revealed nine proteins with significant abundance shifts, suggesting that they could be interesting disease progression markers. These findings highlight specific host protein responses in advanced aspergillosis animals and support the potential of targeted monitoring of plasma biomarkers for earlier, non-invasive diagnosis in falcons. Further validation on a larger cohort is warranted to assess clinical relevance and diagnostic performance in veterinary medicine. SIGNIFICANCE: Aspergillosis remains one of the most significant infectious diseases affecting birds, where delayed diagnosis frequently results in fatal outcomes. Current noninvasive diagnostic is still challenging due to non-specific clinical signs and limited sensitivity and specificity of current diagnostic tests. This study presents a comprehensive proteomic characterization of falcon plasma during aspergillosis, taking advantage of recent advances in high-resolution data-independent acquisition mass spectrometry and the availability of annotated falcon genomes. Comparison of healthy, early, and advanced clinical stages revealed 50 significantly dysregulated proteins, including key acute-phase proteins such as haptoglobin, serum amyloid A, alpha-1-acid glycoprotein, ceruloplasmin, and immunoglobulin light chains. These alterations reflect systemic inflammatory and immune responses to infection and highlight promising biomarkers for early, noninvasive diagnosis. This work contributes to the development of protein-based diagnostic assays, thereby improving clinical management and welfare of captive and wild birds, while also expanding proteomic resources for non-model avian species.