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Isco vs. isca

The Portuguese words isco and isca both mean "bait" and share the same etymological root. The main differences between them are their grammatical gender and their regional usage frequencies in Portugal versus Brazil.

Isco

B2
This is a masculine noun (o isco). It is primarily used in European Portuguese to refer to the organic substance or food used to attract fish or animals. It is rarely used in spoken Brazilian Portuguese.
O pescador colocou o isco no anzol com cuidado.
(The fisherman placed the bait on the hook carefully.)
Precisamos de comprar mais isco antes de sairmos com o barco.
(We need to buy more bait before going out with the boat.)
Um verme vivo é o melhor isco para este tipo de peixe.
(A live worm is the best bait for this type of fish.)

Isca

B2
This is a feminine noun (a isca). It is the standard and most common term in Brazilian Portuguese for any type of bait. In European Portuguese, it is also used, often specifically to refer to artificial lures or individual pieces of prepared bait.
O peixe mordeu a isca e começou a puxar a linha.
(The fish took the bait and started pulling the line.)
Ele usa uma isca artificial que brilha no escuro.
(He uses an artificial bait that glows in the dark.)
Não esqueça de manter a isca fresca dentro do balde.
(Do not forget to keep the bait fresh inside the bucket.)

Summary

To summarize, isco is a masculine word preferred in Portugal for natural bait, while isca is a feminine word that serves as the universal term in Brazil and is also used in Portugal, particularly for artificial lures. Functionally, both attract fish, but you must match the articles (o for isco, a for isca).