Background/Objectives: Postharvest decay of blueberry reflects coupled changes in fruit physiology, host gene expression, and the peel microbiome. We evaluated a hypocrellin-rich fermentation extract (HE) from Hypocrella bambusea and integrated quality, transcriptome, bacterial 16S rRNA, and fungal ITS data to resolve its preservation mechanism, with emphasis on anthocyanin-pathway genes. Methods: Fresh fruit (CK), untreated fruit stored at 25 °C for 6 days (OS), and HE-treated fruit stored under the same conditions (TS) were compared using three matched biological replicates. RNA-seq, bacterial 16S rRNA, fungal ITS, and quality measurements were assigned to the same replicate identifiers (CK_1–CK_3, OS_1–OS_3, and TS_1–TS_3). The supplied normalized expression matrix comprised 9538 genes and nine samples. Log2-transformed expression was analyzed by principal component analysis, exploratory Welch tests with Benjamini–Hochberg correction, homolog-guided GO/KEGG analysis, preranked gene-set enrichment analysis, and Pearson correlations between candidate transcription factors and anthocyanin structural genes. Results: HE descriptively reduced rot index from 70% to 32% and MDA from 8.5 to 5.0 nmol/g FW while improving firmness, soluble solids, titratable acidity, SOD, and POD. PC1 and PC2 explained 78.5% and 16.4% of transcriptomic variation. Relative to OS, TS contained 1872 upregulated and 2934 downregulated genes at FDR < 0.05 and |log2FC| ≥ 1 in the exploratory normalized-expression analysis. Glutathione metabolism, secondary metabolism, hypoxia response, fungal response, and flavonoid biosynthesis were enriched among genes lower in TS. PAL, C4H, 4CL, CHS, F3H/FLS-like, DFR, UFGT, and GST candidates showed strong induction in OS followed by attenuation toward the CK transcriptional state in TS. This pattern is consistent with relief of a storage-induced defense program rather than promotion of anthocyanin accumulation. HE also coincided with depletion of spoilage-associated fungi and restructuring of bacterial communities. Conclusions: HE preservation is best explained as coordinated attenuation of storage-induced metabolic stress, stabilization of anthocyanin-pathway transcriptional homeostasis, and remodeling of the peel microecosystem. Transcript abundance alone does not establish anthocyanin content, and the inferred TF and cross-omics links require promoter, metabolite, raw-count, and sample-level multi-omics validation.
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