Aspergillus fumigatus is an environmental saprophyte and an opportunistic fungal pathogen of the human airway. A. fumigatus can cause a variety of chronic infections, typically in the context of pre-existing lung damage. Animal models of infection are costly and often cannot recapitulate phenotypes observed in patients. The ex-vivo pig lung (EVPL) model was developed for conducting bacterial infection studies as pigs share 90% immunological homology to humans and display many anatomical similarities. EVPL also retains resident immune cells and richer cellular complexity compared to in-vitro models, in addition to a microbiome. Proteomic analysis of A. fumigatus infected alveolar tissue enabled the tracking of molecular changes to the pathogen and the host during the establishment of fungal infection. Analysis identified the metabolism and development of A. fumigatus on the EVPL sections and indicated a shift from initial carbon metabolism to protein metabolism with an emphasis on amino acid metabolism and biosynthesis. The tissue remained responsive to the pathogen with proteins increased in abundance associated with innate immune recruitment at 24 hours, while proteins associated with neutrophil degranulation were decreased in abundance. At 96 hours the infected tissue demonstrated enhanced expression of fibrotic markers relative to the uninfected control. These similarities in response validate the use of this model and contributes supporting evidence that these patterns are of clinical importance during A. fumigatus colonisation and infection of pulmonary tissue.